The long-term objective of this proposal is to determine-the role of modifiers of malonyl-CoA and succinate synthesis and regulators of glutamate dehydrogenase activity in insulin release from pancreatic islets. In general, the research design will be to incubate islets with secretagogues and/or inhibitors of insulin release and measure insulin release plus the levels of key metabolites which can provide insight into the mechanism of insulin release. The methods are the same as we have used previously and involve assays of insulin release and measurement of key metabolites with high pressure liquid chromatography or other standard methods. The results of these studies will further enhance our understanding of insulin release and hopefully lead to better oral hypoglycemic agents for the treatment of diabetes.